Purpose: The current study was conducted in order to investigate the role of Forkhead
box O1 and p21-mediated macrophage polarization in postoperative cognitive dysfunction induced
Methods: There involved a total of 30 healthy mice that were randomly divided into two groups:
control group (without any treatment) and anaesthesia group (treated with sevoflurane inhalation).
The effects of sevoflurane on cognitive function (memory) in mice were studied by trace fear conditioned
reflex, and the effects of systemic inflammation and behavior after operation were measured
by enzyme-linked immunosorbent assay (ELISA), the concentrations of CD163 and tumor
necrosis factor-α (TNF-α) were measured. The expression of macrophage phenotype was
observed by immunofluorescence staining, the expression levels of M1 and M2 markers mRNA
were detected by real-time fluorescence quantitative PCR (RT-PCR), and the expression levels of
FoxO1 and p21 were analyzed by immunoblotting (Western blot).
Results: Compared with the control group, the freezing time in the anesthesia group was lower
than that in the control group (P<0.01), indicating that sevoflurane anesthesia led to the decrease
of cognitive ability. The blood concentrations of CD163 and TNF-α increased significantly at 24 h
after the operation with sevoflurane anesthesia (P<0.05). Fluorescence microscopic observation
showed that M2 was the main type of macrophages in normal tissues, while M1 and M2 phenotypes
were highly expressed in sevoflurane anesthetized tissues at the same time, especially in M1
phenotypes (P<0.01). The polarization of macrophages in the anesthetic group showed the high
level of M1 mRNA, and the expression levels of TNF-α, monocyte chemotactic protein 1(MCP-1)
and Interleukin-6 (IL-6)mRNA in the anesthetic group were significantly higher than those in the
control group (P<0.05). The expression levels of M2 mRNA such as transforming growth factor-β
(TGF-β) and IL-10 were significantly lower than those in the control group (P<0.05). Compared
with the control group, the expression of FoxO1 and p21 protein in the anesthesia group was significantly
lower than that in the control group with a significant statistical difference (P<0.01).
Conclusion: This study offers a theoretical basis and insight for further understanding of the prevention
and treatment of cognitive dysfunction induced by anesthetic drugs.